Albuterol, also referred to as .alpha.-[[(1,1-dimethylethyl)amino]methyl]-4-hydroxy-1,3-benzenedimethanol or as salbutamol, is a .beta.-2 agonist useful as a bronchodilator. It possesses a high degree of selectivity between .beta.-1 receptors (which are present in the heart) and .beta.-2 receptors (which are present in bronchial tissue and elsewhere), for which reason it is widely used in the treatment of asthma, since in therapeutic doses it exhibits fewer cardiac side effects than many other .beta.-agonists.
It is known that among many drugs having chiral centers one enantiomer of a racemic pair is often more active than the other in treating a medical condition. Recent data suggest that the levorotatory R-isomer of albuterol is approximately 80 times more potent than the dextrorotatory S-isomer (Hartley and Middlemis, J. Med. Chem. 14 895-896 (1971)), and preliminary research indicates that administration of the pure R-enantiomer may offer an improved therapeutic ratio.
Methods of producing optically pure albuterol by resolving methyl benzoate albuterol precursors are described only for precursors having the amine protected by a benzyl group. Hartley et al. op. cit. teaches optical resolutions only when both the phenolic group and the amine of the precursor were protected with a benzyl group. The process described by Hartley required the use of expensive starting materials, involved at least 6 independent steps and produced low overall yields. Therefore, there exists a need for a more economical and efficient method of making optically pure albuterol.